Endostatin Adenovirus With Checkpoint Inhibitor in Advanced Head and Neck or Esophageal Cancer

Phase 1Not Yet RecruitingNCT07154108

Sichuan University40 enrolled

Overview

This is a Phase I, open-label, dual-cohort clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of intratumoral injection of recombinant human endostatin adenovirus in combination with a PD-1 inhibitor in patients with recurrent or metastatic head and neck cancer, or in patients with esophageal squamous cell carcinoma (ESCC) with superficial lymph node metastasis.

Cohort A will enroll patients with recurrent or metastatic head and neck cancer. Cohort B will enroll patients with ESCC with superficial lymph node metastasis. Both cohorts will receive intratumoral injection of recombinant human endostatin adenovirus combined with intravenous an immune checkpoint inhibitor. The primary objectives are to assess the safety profile, incidence of dose-limiting toxicities (DLTs), and treatment-related adverse events (TRAEs) of the combination therapy. The secondary objectives include evaluation of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Each cohort plans to enroll approximately 20 patients, with a total of 40 participants.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Esophageal Cancer Head and Neck Cancer (H&Amp;Amp;Amp;N)

Interventions

recombinant human endostatin adenovirusBIOLOGICAL

Recombinant Human Endostatin Adenovirus: Administered via intratumoral injection twice every 3 weeks for a total of eight doses, or until disease progression, the occurrence of unacceptable toxicity, or death from any cause, whichever occurs first.

PD-1 InhibitorDRUG

PD-1 inhibitor: Administered via intravenous infusion once every 3 weeks.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

* Cohort A (Head and Neck Cancer) * Cohort B (Esophageal Squamous Cell Carcinoma) Inclusion Criteria: 1. Age ≥18 years * Cohort A (Head and Neck Cancer): ≤70 years * Cohort B (Esophageal Squamous Cell Carcinoma): ≤75 years 2. Histologically or cytologically confirmed recurrent or metastatic: * Cohort A: Head and Neck Cancer * Cohort B: ESCC, AJCC 9th edition stage IV 3. Prior treatment: * Cohort A: ≥1 prior platinum-based chemotherapy regimen or platinum-refractory/intolerant * Cohort B: Prior immune checkpoint inhibitor (ICI) therapy with documented acquired resistance after prior PR or SD 4. At least one lesion accessible for intratumoral injection * Cohort A: measurable lesion ≥2 cm by RECIST 1.1 * Cohort B: superficial metastatic lymph nodes (cervical or supraclavicular) 5. ECOG performance status * Cohort A: 0-2 * Cohort B: 0-1 6. Adequate organ function 7. Life expectancy ≥12 weeks (Cohort A) 8. No anti-tumor therapy (chemotherapy, radiotherapy, biotherapy, antiviral) within 4 weeks prior to enrollment (Cohort A) 9. Availability of fresh tumor tissue specimen or pathological slides from the injection target lesion (Cohort B) 10. Male/female patients of childbearing potential must use effective contraception during study and for at least 6 months after treatment 11. Voluntary participation with signed informed consent Exclusion Criteria: 1. Known allergy or hypersensitivity to study drugs 2. Lesions unsuitable for injection due to proximity to major blood vessels, nerves, or hollow organs, or with extensive necrosis 3. Deeply located lesions with high procedural difficulty (Cohort B) 4. Concurrent radiotherapy to target lesion(s) (Cohort A) 5. Prior anti-angiogenic therapy (Cohort A) 6. Immunosuppressive therapy or systemic corticosteroids \>10 mg/day prednisone (or equivalent) within 2 weeks prior to enrollment 7. Active autoimmune disease or history of autoimmune disease 8. Congenital or acquired immunodeficiency 9. Severe coagulopathy, bleeding tendency, or high-risk lesions (Cohort B) 10. Poor nutritional status (Cohort B) 11. Interstitial lung disease with symptoms or radiographic evidence (Cohort B) 12. Severe uncontrolled systemic disease or recent myocardial infarction (\<3 months) 13. Acute infection 14. Pregnancy or breastfeeding 15. Other malignancy besides ESCC (Cohort B) 16. Patients unlikely to comply with follow-up or participation requirements 17. Any condition deemed unsuitable for enrollment by the investigator

Locations (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Outcomes

Primary Outcomes

Incidence of treatment-related adverse effects (TRAEs)

This study will collected any adverse medical events that occurred during the study drug treatment, and the treatment related adverse events as assessed by CTCAE v5.0.

Time frame: Through study completion, an average of 1.5 year

Incidence of Dose-Limiting Toxicities (DLTs)

DLTs are defined as treatment-related adverse events occurring during the DLT evaluation period that meet protocol-specified criteria for severity and duration, as assessed by NCI CTCAE v5.0.

Time frame: During the first cycle of treatment （21 days）

Secondary Outcomes

Objective Response Rate (ORR)

It is defined as the proportion of patients with complete response (CR) or partial response (PR), as assessed by RECIST 1.1.

Time frame: up to 12 months

Disease Control Rate (DCR)

DCR refers to the proportion of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) for a specified minimum duration after treatment, based on RECIST 1.1.

Time frame: up to 12 months

Progression-Free Survival (PFS)

Time from the start of treatment to the first documentation of disease progression based on RECIST 1.1.

Time frame: up to 12 months

Overall Survival (OS)

Time from the start of treatment to death from any cause

Time frame: up to 24 months

Central Contacts

Zhenyu Ding, MD

CONTACT

+862885422562 dingzhenyu@scu.edu.cn

Data from ClinicalTrials.gov

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